Inactivated vaccines Inactivated vaccines have been in use since the 1880s. The viruses in these vaccines have been rendered inactive by chemical treatment, as with SARS-CoV-2 candidate vaccines, or by physical treatment. With this type of vaccine, the immune system encounters the virus in its entirety. It can mount a defence when it detects the viral spike protein (also called spicule or S-protein), envelope and nucleoprotein. Currently, seven inactivated vaccine candidates are being tested in humans. Of these, three are in Phase 3 clinical trials. Unlike Phase 1 and Phase 2, which are used to evaluate a vaccine’s tolerability, safety and ability to induce an immune response, a Phase 3 clinical trial allows scientists to test its efficacy. Recombinant proteins Recombinant protein vaccines fall into two categories: subunit and virus-like particle vaccines. For subunit protein vaccines, a viral protein is produced in large quantities in a living “factory,” such as a bacterium, plant, mammalian or insect cell. When the viral protein is presented to the immune system, it triggers a reaction. The 13 subunit vaccine candidates currently in Phase 1, 2 or 3 clinical trials are composed of either the entire spike protein or a specific portion of the spike protein called the ‘receptor binding domain’. Virus-like particle vaccines are composed of a set of viral proteins that mimic the shape of the virus. This particle “pseudo-virus” is an empty shell, devoid of genetic material and non-infectious, but this does not prevent the immune system from recognizing it. Viral vector vaccines This approach is based on using a virus that is non-pathogenic or of little danger to humans. In the case of the 12 vaccine candidates of this type currently being studied in humans, the viral vectors are mostly adenoviruses. They represent a large group of viruses that can cause colds and conjunctivitis, among other symptoms. Used as Trojan horses, these viruses are modified to express the SARS-CoV-2 spike protein following vaccination. Viral vector vaccines are a recent strategy, but were used in the development of the Ebola virus vaccine. RNA and DNA vaccines Despite differences in their composition, DNA and mRNA (messenger RNA) both contain genetic information for protein production. While an RNA molecule can directly produce that information, DNA requires an intermediate transcription step. RNA or DNA vaccine candidates differ from other strategies in two ways. First, it is a novel strategy: there is no RNA or DNA vaccine on the market. Second, they are the only vaccine candidates composed solely of genetic material. In the case of RNA vaccines, messenger RNA molecules are wrapped in lipid nanoparticles. Once the vaccine is injected, the RNA serves as a template for the body’s cells to produce a viral protein — the spike protein, to be precise. DNA vaccines, on the other hand, are made up of a circular DNA (called a plasmid). This DNA will be transcribed into RNA, which will again serve as a template. Six RNA vaccine candidates are currently being tested in humans, two of which are in Phase 3. The five DNA vaccine candidates are in Phase 1 and 2 clinical trials